TOPLINE:

Treatment with elexacaftor-tezacaftor-ivacaftor significantly improved blood glucose regulation in patients with cystic fibrosis and abnormal glucose tolerance, without any safety concerns. It also reduced A1c levels and sweat chloride concentrations over time.

METHODOLOGY:

• Researchers conducted a phase 3b open-label trial at multiple sites in Australia and the European Union to assess the effect of elexacaftor-tezacaftor-ivacaftor, an approved medication for cystic fibrosis, on glucose tolerance in patients with cystic fibrosis.
• Overall, 69 patients (mean age at baseline, 25.1 years; 55.1% men) with either impaired glucose tolerance or cystic fibrosis-related diabetes were enrolled to received elexacaftor-tezacaftor-ivacaftor for 48 weeks.
• The primary endpoint was the change from baseline to the average of weeks 36 and 48 in 2-hour blood glucose levels measured during an oral glucose tolerance test.
• Secondary endpoints included improvements in dysglycemia categorization (including normal glucose tolerance, impaired glucose tolerance, and cystic fibrosis-related diabetes) at week 48 and safety assessment.

TAKEAWAY:

• Treatment with elexacaftor-tezacaftor-ivacaftor led to a significant reduction in 2-hour blood glucose levels from baseline to the average of weeks 36 and 48 following an oral glucose tolerance test (mean difference, -35.0 mg/dL; P < .0001).
• Among 53 participants with abnormal glucose tolerance at baseline, 37.7% (95% CI, 24.8%-52.1%) showed improvements in dysglycemia categorization over week 48.
• At week 48, A1c level dropped by -0.16%, and sweat chloride level decreased by 48.7 mmol/L from baseline, showing better glycemic control and enhanced cystic fibrosis transmembrane conductance regulator function.
• Most adverse events were mild or moderate in severity, and the most common adverse events included COVID, headache, pyrexia, and nasopharyngitis.

IN PRACTICE:

“These results, which are consistent with those previously reported in smaller observational studies, support the potential for ELX/TEZ/IVA [elexacaftor-tezacaftor-ivacaftor] treatment to positively impact glucose regulation and tolerance in people with CF [cystic fibrosis] with early IGT/CFRD [impaired glucose tolerance/cystic fibrosis-related diabetes], providing sustained and clinically meaningful benefits that lead to improved glucose homeostasis over time,” the authors of the study wrote.

SOURCE:

This study was led by Isabelle Durieu, Hospices Civils de Lyon in Lyon, France. It was published online on August 11, 2025, in the American Journal of Respiratory and Critical Care Medicine.

LIMITATIONS:

The open-label design and lack of a comparator group limited the interpretation of efficacy and safety results. Although the study demonstrated significant improvements in endocrine pancreatic function in the study cohort, it could not determine whether these changes were secondary to improved lung health and reduced inflammation or whether they had a direct effect on glucose metabolism.

DISCLOSURES:

This study was funded by Vertex Pharmaceuticals. Five authors reported being employees or former employees of Vertex Pharmaceuticals and possibly owning stock or stock options in the company. Some authors reported having financial and other ties with Vertex Pharmaceuticals, with one author also reported being on the board of the European Cystic Fibrosis Society.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.